Diabetic Retinopathy Editorial September 2012

David Yorston MD
Constultant Ophthalmologist
Tennent Institute of Ophthalmology, Gartnavel Hospital,1053 Great Western Road, Glasgow G12 0YN, UK.

Versión en español aquí: Editorial Retinopatía Diabética

It is ironic that, after a decade of social and economic progress that has almost eliminated hunger from much of Latin America, one of the greatest threats to health in the region is now type 2 diabetes. The number of people with diabetes in the region is growing rapidly. In 2011 there were about 12.5 million people with diabetes in Brazil. By 2030 it is likely that there will be 19.5.million. In Mexico there were 10 million people with diabetes in 2011, but this is likely to increase to 16.5 million by 2030.

Every ophthalmologist in Latin America is aware of the problems caused by diabetic retinopathy, and the increasing numbers of people who require surveillance and treatment.

We are now beginning to get more detailed information on the size of the problem. A recent population-based survey in Chiapas state in S. Mexico found a prevalence of diabetes of 21% in the population aged 50 or over. 39% of people with diabetes had some diabetic retinopathy, 9% had proliferative retinopathy, and 16% had maculopathy. Only 47% of diabetic patients were aware that they needed to have their eyes checked, and only 16% of those who needed laser treatment had been treated. 8% of blindness in this population was due to diabetic retinopathy1.

What can we do to reduce the incidence of blindness caused by diabetic retinopathy?

Primary prevention

Obviously the best way to avoid diabetic retinopathy is to avoid diabetes! Eye care workers can help to reinforce public health messages concerning healthy eating, exercise, and avoiding obesity. Our patients need to know that being overweight may lead to blindness.

People who do develop type 2 diabetes can reduce their risk of retinopathy by tight control of both blood sugar and blood pressure2;3. However, it is important to note that good control of blood sugar does not eliminate the risk of retinopathy, but merely reduces it. If a patient with diabetes does develop retinopathy, we should not blame them for not managing their diabetes well, as even patients with good control of blood sugar may go on to develop retinopathy4. Although ophthalmologists are not responsible for managing their patients’ diabetes and blood pressure, we can support the work of the diabetologists by emphasising the visual benefits of good diabetic control.

Secondary prevention

Diabetic retinopathy may become very advanced before it causes any symptoms. In general, once vision is lost as a result of diabetic retinopathy, it is unlikely to be regained. This means that the best strategy for preventing blindness is to detect and treat diabetic retinopathy at an early stage before it causes loss of vision. As early retinopathy is asymptomatic, this means that some form of screening programme is needed. The best screening method is fundus photography – taking one or two pictures of the retina with a digital fundus camera. These images can be examined immediately, or they can be transmitted to a reading centre. Fundus photos alone are not always sufficient for an exact diagnosis, but they are sufficient to categorise eyes as low risk or high risk, and to separate those patients who should be seen by an ophthalmologist from those who are unlikely to require any treatment5.

In a country like the UK, with a single National Health Service, a screening programme is relatively simple to organise. In Latin America, with fragmented health care systems that mix government, insurance, and privately funded care, it is much harder. The first requirement for any screening programme is to know who has diabetes. In the absence of a national diabetes register, it may be difficult to find out. Health insurers, pharmacies, hospitals, and endocrinologists will all know some of the diabetic patients, but it is unlikely that any one source will know all of them. Secondly, the screening programme has to be able to contact the patients and call them for screening. The photos have to be read by trained staff. In the UK, graders – who are not ophthalmologists – are trained simply to distinguish between normal and abnormal photos. The ophthalmologists only examine the pictures graded as abnormal. In order to be sure that the screening programme is accurate, quality control is essential, so some of the normal photos should be re-examined by another ophthalmologist to check that the grading is accurate. If people do not come for their screening appointment, the programme needs a mechanism to follow them up. If significant retinopathy is detected at screening, the patient must be referred to a clinic that has the capacity to examine the retina and treat the retinopathy.

There will be few countries in Latin America that have the resources to set up an effective and reliable national screening programme for diabetic retinopathy. However, it may well be possible to develop local programmes by collaborating with other health workers involved in the care of diabetes. These include not only the doctors who treat diabetes, but also the insurers and social security systems that pay for treatment, organisations of patients with diabetes, and other health care workers such as pharmacists, dieticians, and nurses.

Tertiary prevention

Fortunately we now have very effective treatments for most forms of diabetic retinopathy. Recent research has focused mostly on diabetic maculopathy.

Maculopathy occurs as a result of damage to the retinal capillaries which then leak fluid, causing the retina to become swollen and oedematous. Chronic leakage leads to the build up of fatty deposits in the retina, called exudates. These are visible in fundus photos. The usual treatment of maculopathy has, since the 1980’s, been laser. The Early Treatment Diabetic Retinopathy Study showed that the risk of loss of vision could be halved by laser treatment, however, only a small proportion of patients achieved any improvement in their sight. There are now a number of alternative treatment options, most of which have been shown to be superior to laser. Monthly injections of ranibizumab were superior to laser treatment in several trials6-9. More patients gained vision with injections of anti-VEGF than with laser treatment. However, ranibizumab is very expensive, and it is not easy to organise monthly intraocular injections for large numbers of people.

Steroid injections are much less costly, and in the short term are effective, however, after two years, laser is more effective than steroid injections10. Steroid implants of fluocinolone acetonide that release a very small does of steroid into the eye over a several months have been shown to be superior to laser treatment at two years, but they have significant side-effects, with over 70% of patients requiring cataract surgery, and nearly 5% developing complications related to elevated intraocular pressure. The steroid implants, although easier to deliver than monthly ranibizumab, are also expensive11.

A less costly alternative is bevacizumab (Avastin) This is already widely used in Latin America. The BOLT study compared macular laser treatment (MLT) with intravitreal bevacizumab injections delivered as required over a two year period. At two years, the bevacizumab treated eyes had required a median of thirteen injections, and had gained a mean of 8.6 letters on the ETDRS chart. The MLT group required a median of four laser treatments, and suffered a mean loss of 0.5 letters (p<0.001). An additional advantage of bevacizumab, as used in this study, is that patients were reviewed every six weeks, rather than every four weeks, which reduces costs substantially12;13.

Unfortunately many of these new treatments require the use of optical coherence tomography to detect and monitor oedema of the fovea. This technology is expensive, and is not widely available in Latin America outside major urban centres.

The management of proliferative diabetic retinopathy has seen fewer innovations, partly because the standard treatment with pan-retinal laser is so effective. Some patients with severe proliferative retinopathy have poor outcomes despite laser, and this is sometimes due to inadequate treatment. At least half of the peripheral retina should be treated. In patients with vitreous haemorrhage, or cataract, not every laser pulse results in an effective retinal burn. The end-point of pan-retinal laser should be judged by looking at the retina rather than the counter on the laser!

Even if adequate pan-retinal laser is delivered, some patients will develop vitreous haemorrhage or traction retinal detachment, and will require vitrectomy. Diabetic vitrectomy is now a relatively safe procedure, with good outcomes. Although the capital cost of equipment for vitrectomy is high, the benefits of surgery are sufficient to make diabetic vitrectomy a very cost-effective procedure14;15

Although the evidence is contradictory, pre-operative intravitreal bevacizumab appears to reduce the risk of complications in diabetic vitrectomy, particularly when there has been inadequate pre-operative laser, which is often the case in low and middle income countries16;17. Intravitreal bevacizumab can promote fibrosis and contraction of retinal membranes, leading to retinal detachment, so it should be given no more than one week prior to surgery.

Conclusion

Diabetic retinopathy poses a major challenge to Vision2020 in Latin America. Unlike cataract, or glaucoma, which can be dealt with by eye care professionals alone, managing diabetic retinopathy requires building alliances with diabetologists, cardiologists, public health specialists, health care providers and civil society. If we are willing to leave our comfort zone, and engage with our fellow professionals in these related disciplines, we can prevent the great majority of visual impairment caused by diabetes.

Reference List

1. Polack S, Yorston D, Lopez-Ramos A, Lepe-Orta S, Baia RM, Alves L et al. Rapid assessment of avoidable blindness and diabetic retinopathy in Chiapas, Mexico. Ophthalmology. 2012;119:1033-40.

2. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ 1998;317:703-13.

3. UKPDS. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:837-53.

4. Lewis K, Patel D, Yorston D, Charteris D. A qualitative study in the United Kingdom of factors influencing attendance by patients with diabetes at ophthalmic outpatient clinics. Ophthalmic Epidemiol. 2007;14:375-80.

5. Ockrim Z,.Yorston D. Managing diabetic retinopathy. BMJ 2010;341:c5400.

6. Elman MJ, Aiello LP, Beck RW, Bressler NM, Bressler SB, Edwards AR et al. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology 2010;117:1064-77.

7. Mitchell P, Bandello F, Schmidt-Erfurth U, Lang GE, Massin P, Schlingemann RO et al. The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology. 2011;118:615-25.

8. Nguyen QD, Shah SM, Khwaja AA, Channa R, Hatef E, Do DV et al. Two-year outcomes of the ranibizumab for edema of the mAcula in diabetes (READ-2) study. Ophthalmology. 2010;117:2146-51.

9. Nguyen QD, Brown DM, Marcus DM, Boyer DS, Patel S, Feiner L et al. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology. 2012;119:789-801.

10. Beck RW, Edwards AR, Aiello LP, Bressler NM, Ferris F, Glassman AR et al. Three-year follow-up of a randomized trial comparing focal/grid photocoagulation and intravitreal triamcinolone for diabetic macular edema. Arch.Ophthalmol. 2009;127:245-51.

11. Campochiaro PA, Brown DM, Pearson A, Chen S, Boyer D, Ruiz-Moreno J et al. Sustained Delivery Fluocinolone Acetonide Vitreous Inserts Provide Benefit for at Least 3 Years in Patients with Diabetic Macular Edema. Ophthalmology. 2012.

12. Michaelides M, Kaines A, Hamilton RD, Fraser-Bell S, Rajendram R, Quhill F et al. A prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (BOLT study) 12-month data: report 2. Ophthalmology. 2010;117:1078-86.

13. Rajendram R, Fraser-Bell S, Kaines A, Michaelides M, Hamilton RD, Esposti SD et al. A 2-Year Prospective Randomized Controlled Trial of Intravitreal Bevacizumab or Laser Therapy (BOLT) in the Management of Diabetic Macular Edema: 24-Month Data: Report 3. Arch.Ophthalmol. 2012.

14. Yorston D, Wickham L, Benson S, Bunce C, Sheard R, Charteris D. Predictive clinical features and outcomes of vitrectomy for proliferative diabetic retinopathy. Br J Ophthalmol 2008;92:365-8.

15. Gupta B, Sivaprasad S, Wong R, Laidlaw A, Jackson TL, McHugh D et al. Visual and anatomical outcomes following vitrectomy for complications of diabetic retinopathy: the DRIVE UK study. Eye (Lond) 2012;26:510-6.

16. Ahmadieh H, Shoeibi N, Entezari M, Monshizadeh R. Intravitreal bevacizumab for prevention of early postvitrectomy hemorrhage in diabetic patients: a randomized clinical trial. Ophthalmology 2009;116:1943-8.

17. da RL, Ribeiro JA, Costa RA, Barbosa JC, Scott IU, Figueiredo-Pontes LL et al. Intraoperative bleeding during vitrectomy for diabetic tractional retinal detachment with versus without preoperative intravitreal bevacizumab (IBeTra study). Br J Ophthalmol 2009;93:688-91.

 

 

 

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